Description: The Risk Factors project has studied the very large HIV epidemic among injecting drug users (IDUs) in New York City from 1978 (using stored sera) to the present. HIV spread rapidly among lDUs in NYC reaching 50% prevalence by the time AIDS was discovered in 1981 and leading to over 50,000 cases of AIDS among lDUs in the city, almost 10% of all AIDS cases in the US. In the early 1990s, HIV prevention programs for IDUs were greatly expanded, and NYC has become one of the most important success stories in HIV prevention for IDUs. Since the early 1990s, HIV incidence among lDUs has declined from 5/100 person-years (py) to 1-2/ 100 py, and prevalence has declined from 50% to under 15% (a level not seen since 1978-79). There are still very important questions to be answered in this current prevention success story: (1) How far will declines in prevalence and incidence continue before a stable endemic situation develops? (2) There are currently substantial differences in prevalence among racial/ethnic groups--25% among Blacks vs. 5% among Whites, and 8% among Hispanics. Will prevention be successful for all racial/ethnic groups, or will the current differences persist indefinitely? (3) Now that injection-related HlV transmission has been greatly reduced, to what extent will continuing HIV infection be driven by sexual transmission? and (4) Will the success in reducing HIV also lead to success in reducing hepatitis C among lDUs in NYC? We will address these questions through: (a) continuation of our large-sample cross-sectional survey of risk behavior, social network factors, utilization of prevention services, HIV prevalence and HIV incidence (STAHRS testing); (b) mathematical modeling of HIV and STI transmission among lDUs and NIDUs; (c) exploratory testing of genetic differences of HIV strains among different racial ethnic groups in NYC; (d) large-sample HCV prevalence surveys, and (e) quantitative research syntheses of our data with other studies conducted on IDUs and NlDUs in NYC. The proposed research will provide information of great scientific interest and public health importance regarding the ability of prevention programs to control high HIV and HCV sero-prevalence epidemics, explaining racial ethnic differences in HIV infection, and examining sexual transmission of HIV among both lDUs and NIDUs.